In one of the most closely-watched medical races of all time, Amgen and rival pharmaceutical companies are chasing approval for new anti-cholesterol drugs that have the potential to be blockbusters.
Cardiologists see them as the single most promising class of drugs currently in development, said Dr. Steven Nissen, the department chair of cardiovascular medicine at the Cleveland Clinic. For its new cholesterol-fighting drug, AMG 145, Thousand Oaks-based Amgen expects to have data from its pre-marketing clinical trial period available in early 2014.
"We're neck and neck with our competitors," said Scott Wasserman, Amgen's global development lead for cardiovascular medicines.
AMG 145 dramatically cuts low-density lipoproteins (LDL) levels by mimicking rare genetic mutations that inhibit a protein called PCSK9 that infringes on the liver's ability to remove bad cholesterol from the blood. The developing drugs grab hold of the PCSK9 protein and disable it.
Cholesterol is a waxy substance in the body that helps digest foods, and makes hormones and vitamin D. Two kinds of lipoproteins carry cholesterol throughout the body: high-density lipoproteins (HDL) and LDL, which is considered bad because it can build up in your arteries.
Nissen, a leader of an Amgen trial, said chances are high that the U.S. Food and Drug Administration will approve PCSK9 inhibitors in the next few years, providing an option for patients who aren't benefiting from cholesterol-regulating statins, which are widely used but increasingly ineffective, according to researchers.
"We have a lot of patients who have very high cholesterol levels who either can't take a statin or it doesn't lower their LDL enough," Nissen said.
Early-stage trial results for AMG 145 were released last year and patients studied had high cholesterol and were taking statins. After monthly injections with AMG 145, their cholesterol levels were reduced 66 percent.
By combining statins and PCSK9 inhibitors, chances are that virtually 100 percent of patients will be treatable, Nissen said.
One question still being studied is: Can LDL levels fall too low?
"Everybody's worried about that," Nissen said. "It's probably not a problem but it remains to be proven beyond a reasonable doubt."
"Frankly at this stage we don't know how low to go to be able to provide a benefit," said Wasserman, a cardiologist by training. "But I think our clinical development program is taking a very step-wise approach."
It's a cautious and measured approach, and academics and regulators have been reassuring, Wasserman said.
AMG 145 will likely be manufactured in Rhode Island, where it's now being produced for clinical trials, said Amgen spokeswoman Ashleigh Koss. "And as you may be aware, several of our products are filled and finished in Puerto Rico."
Wasserman stressed, however, that Amgen's people in Thousand Oaks are playing a significant role in moving the therapy ahead.
"A lot of effort and a lot of people here put in extra hours and have done a fabulous job of really helping the program move forward," he said. "There's been a lot of Ventura County spirit in this and the success of this molecule will reflect well on Ventura County."
If AMG 145 becomes a blockbuster it could help fill in sales gaps left by Aranesp and Epogen, Amgen's anemia treatments that were once principal products but suffered declines after safety issues arose in recent years. Furthermore, Amgen will lose exclusivity
on Epogen when its last U.S. patent expires in May 2015. The last U.S. patent for Aranesp expires in May 2024.
Meanwhile, the market for PCSK9-inhibitors is growing. RBC Capital Markets analyst Adnan Butt pegs it at more than $9 billion.
The usage of cholesterol-lowering medication in America is certainly on the rise. It went from 5 percent in 1988--1994 to 23 percent in 2007--2010, according to the National Center for Health Statistics. Recent advances in medical treatment have not managed to snuff out high cholesterol issues in the United States, NCHS reported in March. More than one-quarter of adults aged 40 to 74 have high cholesterol nationwide.
And the problem isn't limited to the United States. In most countries it's a major public health issue contributing to cardiovascular disease, the leading cause of death among men and women. Although various treatments are available for lowering cholesterol, it's estimated that two-thirds of treated high-risk patients are unable to control it.
Shareholder Steve Silverman is pleased to see Amgen making room in its pipeline for heart medicine.
"It shows diversity within their domain of medicine," he said.
Wasserman said it's not yet known how much it might cost for patients to be treated with AMG 145.
Amgen's competitors are Sanofi and its partner Regeneron, and Pfizer.
Sanofi and Regeneron anticipate initial launch of their drug -- alirocumab -- at the end of 2015. They will then have a global launch in 2016, according to a Sanofi spokeswoman.
Pfizer presented data concerning its drug, RN316, in November during the American Heart Association Scientific Sessions. The company does not have an anticipated launch date, said Pfizer spokesman MacKay Jimeson. ___